The objective of this project is the understanding of the mechanisms which regulate the respiratory function of blood at molecular, cellular, and physiologic levels. The oxygenation of normal human hemoglobin, variant human hemoglobins, and hemoglobins of animals are studied, along with the cellular factors which modify these properties. The ultimate objective of the project is to understand the relationships among these properties, pulmonary gas exchange and tissue oxygen demands, under normal and pathologic conditions. A systematic characterization of the properties of normal blood will be continued; the availability of the new equipment renders existing data obsolete. Additional human hemoglobin variants may be studied. Of special interest is the compensatory mechanisms which are employed by subjects with high affinity hemoglobins. The characterization of the role of hemoglobin C in the adaptation of sheep and goats to their environment will be pursued. Other animals with unique environmental demands might be studied also. New equipment is being designed by the Laboratory of Technical Development which will enable the study of the kinetic properties of blood oxygenation and deoxygenation. It is hoped that this study will lead to better understanding of the relationships between capillary blood flow and oxygenation which occurs in vivo.